What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).

Palicelli, A and Croci, S and Bisagni, A and E, Zanetti and D, De Biase and B, Melli and F, Sanguedolce and M, Ragazzi and M, Zanelli and A, Chaux and S, Cañete-Portillo and MP, Bonasoni and A, Soriano and S, Ascani and M, Zizzo and C, Castro Ruiz and A, De Leo and G, Giordano and M, Landriscina and G, Carrieri and L, Cormio and DM, Berney and J, Gandhi and G, Santandrea and M, Bonacini

International journal of molecular sciences (2021) 22:

Link: https://pubmed.ncbi.nlm.nih.gov/34830179/

Abstract

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).

Citation

Palicelli, A., Croci, S., Bisagni, A., E, Z., D, D. B., B, M., F, S., M, R., M, Z., A, C., S, C.-P., MP, B., A, S., S, A., M, Z., C, C. R., A, D. L., G, G., M, L., … M, B. (2021). What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models). International Journal of Molecular Sciences, 22(22). https://pubmed.ncbi.nlm.nih.gov/34830179/ Animals, Male, Humans, Mice, Cell Line, Tumor, Immunotherapy/*methods, *Disease Models, Animal, Signal Transduction/genetics/*immunology, Prostatic Neoplasms, B7-H1 Antigen/genetics/*immunology/metabolism, Gene Expression Regulation, Neoplastic/immunology, Prostatic Neoplasms/genetics/immunology/*therapy

Keywords

• Animals
• Male
• Humans
• Mice
• Cell Line
• Tumor
• Immunotherapy/*methods
• *Disease Models
• Animal
• Signal Transduction/genetics/*immunology
• Prostatic Neoplasms
• B7-H1 Antigen/genetics/*immunology/metabolism
• Gene Expression Regulation
• Neoplastic/immunology
• Prostatic Neoplasms/genetics/immunology/*therapy